1. Field of the Invention
The invention relates generally to prodrugs and more specifically to water-soluble derivatives of 2,6-diisopropylphenol (Propofol).
2. Background Information
2,6-diisopropylphenol is highly lipophilic and is practically insoluble in water. For intravenous applications, it is formulated in water using a variety of solubilizing agents and/or emulsifiers. Examples of such formulations include Cremophor™, Intralipid™, Diprivan™, Disoprofol™, Disoprivan™, and Rapinovet™. The aforementioned formulations have many limitations. They cause allergic side effects and pain upon injection. Their preparation is difficult and costly and most importantly they cannot be sterilized and hence anti-microbial agents must be added to the formulations.
Propofol or 2,6-diisopropylphenol is a short acting anesthetic that is administered intravenously (i.v.) to mammalian subjects. The low water solubility of this compound presents a significant formulation challenge. The currently approved mode of administration for Propofol is an emulsion that has many disadvantages including costly preparation and sterilization procedures. Oxidation of Propofol to unwanted side-products in the presence of oxygen and light drastically shortens the shelf life of such formulations. In addition, the oil-in-water emulsions cause a number of clinical side effects including pain on injection and pulmonary embolism.
Thus, there exists a clear need for a water-soluble, stable, non-toxic pharmaceutical composition of 2,6-diisopropylphenol.